Assessement of performance of an implanted sensor

ABSTRACT

An analyte monitoring system and method. The analyte monitoring system may include an analyte sensor and a transceiver. The analyte sensor may include an analyte indicator that exhibits one or more detectable properties based on an amount or concentration of an analyte in proximity to the indicator. The transceiver may be configured to receive one or more measurements from the sensor. The transceiver may be configured to assess in real time a performance of the sensor based on at least the one or more measurements. The transceiver may be configured to determine whether the performance of the sensor is deficient based at least on the assessed performance of the sensor. The transceiver may be configured to calculate an analyte level based on at least the one or more sensor measurements. The transceiver may be configured to determine whether the calculated analyte level is a spike.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a divisional of U.S. application Ser. No.16/709,225, filed on Dec. 10, 2019, which claims the benefit of priorityto U.S. Provisional Application Ser. No. 62/777,591, filed on Dec. 10,2018, which are incorporated herein by reference in their entireties.

BACKGROUND Field of Invention

Aspects of the present invention relate to analyte monitoring, assessingin real time sensor performance, and determining whether sensorperformance is no longer suitable for analyte monitoring.

Discussion of the Background

The prevalence of diabetes mellitus continues to increase inindustrialized countries, and projections suggest that this figure willrise to 4.4% of the global population (366 million individuals) by theyear 2030. Glycemic control is a key determinant of long-term outcomesin patients with diabetes, and poor glycemic control is associated withretinopathy, nephropathy and an increased risk of myocardial infarction,cerebrovascular accident, and peripheral vascular disease requiring limbamputation. Despite the development of new insulins and other classes ofantidiabetic therapy, roughly half of all patients with diabetes do notachieve recommended target hemoglobin A1c (HbA1c) levels <7.0%.

Frequent self-monitoring of blood glucose (SMBG) is necessary to achievetight glycemic control in patients with diabetes mellitus, particularlyfor those requiring insulin therapy. However, current blood(finger-stick) glucose tests are burdensome, and, even in structuredclinical studies, patient adherence to the recommended frequency of SMBGdecreases substantially over time. Moreover, finger-stick measurementsonly provide information about a single point in time and do not yieldinformation regarding intraday fluctuations in blood glucose levels thatmay more closely correlate with some clinical outcomes.

Continuous glucose monitors (CGMs) have been developed in an effort toovercome the limitations of finger-stick SMBG and thereby help improvepatient outcomes. These systems enable increased frequency of glucosemeasurements and a better characterization of dynamic glucosefluctuations, including episodes of unrealized hypoglycemia.Furthermore, integration of CGMs with automated insulin pumps allows forestablishment of a closed-loop “artificial pancreas” system to moreclosely approximate physiologic insulin delivery and to improveadherence.

Monitoring real-time analyte measurements from a living body viawireless analyte monitoring sensor(s) may provide numerous health andresearch benefits. There is a need to enhance such analyte monitoringsystems via innovations comprising, but not limited to, the ability toassess the performance of an analyte sensor in an analyte monitoringsystem.

SUMMARY

One aspect of the invention may provide an analyte monitoring systemincluding an analyte sensor and a transceiver. The analyte sensor mayinclude an indicator that exhibits one or more detectable propertiesbased on an amount or concentration of an analyte in a first medium inproximity to the indicator. The transceiver may be configured to (i)receive one or more sensor measurements from the analyte sensor, (ii)assess a performance of the analyte sensor based on at least one or moreof the received one or more sensor measurements, (iii) determine whetherthe performance of the analyte sensor is deficient based at least on theassessed performance of the analyte sensor, and (iv) if the performanceof the analyte sensor is determined to be deficient, display a sensorretirement indication.

In some aspects, the analyte monitoring system may further include adisplay device, the transceiver may be configured to display the sensorretirement indication by conveying a sensor retirement communication tothe display device, and the display device may be configured to receivethe sensor retirement communication and, in response to receiving thesensor retirement communication, display an indication that the analytesensor needs to be replaced.

In some aspects, the transceiver may be further configured to calculatean analyte level using at least one or more of the received one or moresensor measurements and, only if the performance of the analyte sensoris not determined to be deficient, display the calculated analyte level.In some aspects, the transceiver may further include a display device,the transceiver may be configured to display the calculated analytelevel by conveying the calculated analyte level to the display device,and the display device may be configured to receive and display thecalculated analyte level. In some aspects, the calculated analyte levelmay be a calculation of an amount or concentration of the analyte in asecond medium (“second medium analyte level”). In some aspects, thetransceiver may be configured to calculate an amount or concentration ofthe analyte in the first medium (“first medium analyte level”) using atleast one or more of the received one or more sensor measurements. Insome aspects, the transceiver may be configured to calculate a rate ofchange of the amount or concentration of the analyte in the first medium(“first medium analyte level rate of change”) using at least thecalculated first medium analyte level and one or more previous firstmedium analyte levels. In some aspects, the transceiver may beconfigured to calculate the second medium analyte level using at leastthe first medium analyte level and the first medium analyte level rateof change.

In some aspects, assessing the performance of the analyte sensor mayinclude calculating one or more of a spike metric, a reference channelinstability metric, a diagnostic drift metric, and a reference channeldecrease metric. In some aspects, assessing the performance of theanalyte sensor may include calculating the minimum of two or more of aspike metric, a reference channel instability metric, a diagnostic driftmetric, and a reference channel decrease metric. In some aspects, one ormore of the spike metric, the reference channel instability metric, thediagnostic drift metric, and the reference channel decrease metric maybe weighted.

In some aspects, determining whether the performance of the analytesensor is deficient may include comparing the assessed performance ofthe analyte sensor to a deficiency threshold. In some aspects,determining whether the performance of the analyte sensor is deficientmay include determining whether the assessed performance is below adeficiency threshold for at least a period of time.

Another aspect of the invention may provide a method including receivingone or more sensor measurements from an analyte sensor, and the analytesensor may include an indicator that exhibits one or more detectableproperties based on an amount or concentration of an analyte in a firstmedium in proximity to the indicator. The method may include assessing aperformance of the analyte sensor based on at least one or more of thereceived one or more sensor measurements. The method may includedetermining that the performance of the analyte sensor is deficientbased on at least the assessed performance of the analyte sensor. Themethod may include, as a result of determining that the performance ofthe analyte sensor is deficient, displaying a sensor retirementindication.

In some aspects, displaying the sensor retirement indication may includeconveying a sensor retirement communication to a display device, and themethod may further include using the display device to receive thesensor retirement communication and, in response to receiving the sensorretirement communication, displaying an indication that the analytesensor needs to be replaced.

Still another aspect of the invention may provide a method includingusing a sensor interface of a transceiver to receive one or more firstsensor measurements from an analyte sensor, and the analyte sensor mayinclude an indicator that exhibits one or more detectable propertiesbased on an amount or concentration of an analyte in a first medium inproximity to the indicator. The method may include using a processor ofthe transceiver to calculate a first analyte level using at least one ormore of the received one or more first sensor measurements. The methodmay include using the processor of the transceiver to perform a firstassessment of a performance of the analyte sensor based on at least oneor more of the received one or more first sensor measurements. Themethod may include using the processor of the transceiver to determinethat the performance of the analyte sensor is not deficient based on atleast the first assessment of the performance of the analyte sensor. Themethod may include, as a result of determining that the performance ofthe analyte sensor is not deficient, displaying the calculated firstanalyte level. The method may include using the sensor interface of thetransceiver to receive one or more second sensor measurements from theanalyte sensor. The method may include using the processor of thetransceiver to calculate a second analyte level using at least one ormore of the received one or more second sensor measurements. The methodmay include using the processor of the transceiver to perform a secondassessment of the performance of the analyte sensor based on at leastone or more of the received one or more second sensor measurements. Themethod may include using the processor of the transceiver to determinethat the performance of the analyte sensor is deficient based on atleast the second assessment of the performance of the analyte sensor.The method may include, as a result of determining that the performanceof the analyte sensor is deficient, displaying a sensor retirementindication and not displaying the second analyte level.

In some aspects, displaying the calculated first analyte level mayinclude conveying the calculated first analyte level to a displaydevice, and displaying the sensor retirement indication may includeconveying a sensor retirement communication to a display device. In someaspects, the method may further include using the display device to:receive and display the calculated first analyte level, receive thesensor retirement communication, and, in response to receiving thesensor retirement communication, display an indication that the analytesensor needs to be replaced. In some aspects, the calculated firstanalyte level may be a calculation of an amount or concentration of theanalyte in a second medium (“second medium analyte level”). In someaspects, calculating the second medium analyte level may includecalculating an amount or concentration of the analyte in the firstmedium (“first medium analyte level”) using at least one or more of thereceived one or more sensor measurements. In some aspects, calculatingthe second medium analyte level may include calculating a rate of changeof the amount or concentration of the analyte in the first medium(“first medium analyte level rate of change”) using at least thecalculated first medium analyte level and one or more previous firstmedium analyte levels. In some aspects, calculating the second mediumanalyte level may include calculating the second medium analyte levelusing at least the first medium analyte level and the first mediumanalyte level rate of change.

In some aspects, assessing the performance of the analyte sensor mayinclude calculating one or more of a spike metric, a reference channelinstability metric, a diagnostic drift metric, and a reference channeldecrease metric. In some aspects, assessing the performance of theanalyte sensor may include calculating the minimum of two or more of aspike metric, a reference channel instability metric, a diagnostic driftmetric, and a reference channel decrease metric. In some aspects, one ormore of the spike metric, the reference channel instability metric, thediagnostic drift metric, and the reference channel decrease metric maybe weighted.

In some aspects, determining whether the performance of the analytesensor is deficient may include comparing the assessed performance ofthe analyte sensor to a deficiency threshold. In some aspects,determining whether the performance of the analyte sensor is deficientmay include determining whether the assessed performance is below adeficiency threshold for at least a period of time. In some aspects, themethod may further include performing a spike analysis on the calculatedfirst analyte level. In some aspects, the method may further includeperforming a reference channel instability analysis using at least oneor more received sensor measurements.

Yet another aspect of the invention may provide an analyte monitoringsystem including an analyte sensor and a transceiver. The analyte sensormay include an indicator that exhibits one or more detectable propertiesbased on an amount or concentration of an analyte in a first medium inproximity to the indicator. The transceiver may be configured to receiveone or more first sensor measurements from the analyte sensor. Thetransceiver may be configured to calculate a first analyte level usingat least one or more of the received one or more first sensormeasurements. The transceiver may be configured to receive one or moresecond sensor measurements from the analyte sensor. The transceiver maybe configured to calculate a second analyte level using at least one ormore of the received one or more second sensor measurements. Thetransceiver may be configured to perform a spike analysis to determinewhether the second analyte level is a spike. The transceiver may beconfigured to, if the second analyte level is not determined to be aspike, display the second analyte level. The transceiver may beconfigured to, if the second analyte level is determined to be a spike,calculate and display an alternative second analyte level.

In some aspects, the analyte monitoring system may further include adisplay device, the transceiver may be configured to display the secondanalyte level by conveying the second analyte level to the displaydevice, the display device may be configured to receive and display thesecond analyte level, the transceiver may be configured to display thealternative second analyte level by conveying the alternative secondanalyte level to the display device, and the display device may beconfigured to receive and display the alternative second analyte level.In some aspects, the spike analysis may include calculating an analytelevel rate of change and comparing an absolute value of the analytelevel rate of change to a rate of change threshold. In some aspects, theanalyte level rate of change may be calculated as equal to thedifference between the first and second analyte levels divided by thedifference between time stamps for the first and second analyte levels.

In some aspects, the spike analysis may include calculating a firstanalyte level rate of change for the first analyte level, calculating asecond analyte level rate of change for the second analyte level, andcomparing an absolute value of the difference between the first andsecond analyte level rates of change to a rate of change differencethreshold. In some aspects, calculating the alternative second analytelevel may include calculating one or more of (i) a predicted secondanalyte level using at least the first analyte level and a first analytelevel rate of change for the first analyte level, (ii) athreshold-limited second analyte level using at least the first analytelevel and a rate of change threshold, and (iii) a dynamic Kalmanfiltered second analyte value. In some aspects, calculating thealternative second analyte level may include calculating two or more of(i) a predicted second analyte level using at least the first analytelevel and a first analyte level rate of change for the first analytelevel, (ii) a threshold-limited second analyte level using at least thefirst analyte level and a rate of change threshold, and (iii) a dynamicKalman filtered second analyte value. In some aspects, calculating thealternative second analyte level may include calculating an average oftwo or more of (i) a predicted second analyte level calculated using atleast the first analyte level and a first analyte level rate of changefor the first analyte level, (ii) a threshold-limited second analytelevel calculated using at least the first analyte level and a rate ofchange threshold, and (iii) a dynamic Kalman filtered second analytevalue.

In some aspects, the transceiver may be further configured to: perform aspike analysis to determine whether the first analyte level is a spike,and, if the first analyte level was determined to be a spike, use atleast the second analyte level to determine whether the first analytelevel truly was a spike. In some aspects, the first analyte level may bea calculation of an amount or concentration of the analyte in a secondmedium (“first M2_AL”), and the second analyte level may be acalculation of an amount or concentration of the analyte in the secondmedium (“second M2_AL”). In some aspects, the transceiver may beconfigured to calculate a first amount or concentration of the analytein the first medium (“first M1_AL”) using at least one or more of thereceived one or more first sensor measurements. In some aspects, thetransceiver may be configured to calculate a first rate of change of theamount or concentration of the analyte in the first medium (“firstM1_ROC”) using at least the calculated first M1_AL and one or moreprevious M1_ALs. In some aspects, the transceiver may be configured tocalculate the first M2_AL using at least the first M1_AL and the firstM1_ROC. In some aspects, the transceiver may be configured to calculatea second amount or concentration of the analyte in the first medium(“second M1_AL”) using at least one or more of the received one or moresecond sensor measurements. In some aspects, the transceiver may beconfigured to calculate a second rate of change of the amount orconcentration of the analyte in the first medium (“second M1_ROC”) usingat least the calculated second M1_AL and the calculated first M1_AL. Insome aspects, the transceiver may be configured to calculate the secondM2_AL using at least the second M1_AL and the second M1_ROC. In someaspects, the spike analysis to determine whether the second analytelevel is a spike may include comparing an absolute value of the secondM1_ROC to a rate of change threshold. In some aspects, the second M1_ROCmay be calculated as equal to the difference between the second M1_ALand the first M1_AL divided by the difference between a time stamp forthe second M1_AL and a time stamp for the first M1_AL. In some aspects,the spike analysis to determine whether the second analyte level is aspike may include comparing an absolute value of the difference betweenthe first M1_ROC and the second M1_ROC to a rate of change differencethreshold.

Yet another aspect of the invention may provide a method including usinga sensor interface of a transceiver to receive one or more first sensormeasurements from an analyte sensor, and the analyte sensor may includean indicator that exhibits one or more detectable properties based on anamount or concentration of an analyte in a first medium in proximity tothe indicator. The method may include using a processor of thetransceiver to calculate a first analyte level using at least one ormore of the received one or more first sensor measurements. The methodmay include using the processor of the transceiver to perform a spikeanalysis and determine that the first analyte level is not a spike. Themethod may include using the processor of the transceiver to convey thefirst analyte level to a display device. The method may include usingthe processor of the transceiver to receive one or more second sensormeasurements from the analyte sensor. The method may include using theprocessor of the transceiver to calculate a second analyte level usingat least one or more of the received one or more second sensormeasurements. The method may include using the processor of thetransceiver to perform a spike analysis and determine that the secondanalyte level is a spike. The method may include using the processor ofthe transceiver to calculate an alternative second analyte level. Themethod may include using the transceiver to convey the alternativesecond analyte level to the display device.

Further variations encompassed within the systems and methods aredescribed in the detailed description of the invention below.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and form partof the specification, illustrate various, non-limiting aspects of thepresent invention. In the drawings, like reference numbers indicateidentical or functionally similar elements.

FIG. 1 is a schematic view illustrating an analyte monitoring systemembodying aspects of the present invention.

FIG. 2 is a schematic view illustrating a sensor and transceiver of ananalyte monitoring system embodying aspects of the present invention.

FIG. 3 is a schematic view illustrating a transceiver embodying aspectsof the present invention.

FIG. 4 is a flow chart illustrating an analyte monitoring processembodying aspects of the present invention.

FIG. 5 is a flow chart illustrating a spike analysis process embodyingaspects of the present invention.

FIG. 6 is a flow chart illustrating a process for calculating a metricfor electronic performance embodying aspects of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1 is a schematic view of an exemplary analyte monitoring system 50embodying aspects of the present invention. The analyte monitoringsystem 50 may be a continuous analyte monitoring system (e.g., acontinuous glucose monitoring system). In some aspects, the analytemonitoring system 50 may include one or more of an analyte sensor 100, atransceiver 101, and a display device 105. In some aspects, the sensor100 may be a small, fully subcutaneously implantable sensor that takesone or more measurements indicative of analyte (e.g., glucose) levels ina first medium (e.g., interstitial fluid) of a living animal (e.g., aliving human). However, this is not required, and, in some alternativeaspects, the sensor 100 may be a partially implantable (e.g.,transcutaneous) sensor or a fully external sensor.

In some aspects, the transceiver 101 may be an externally worntransceiver (e.g., attached via an armband, wristband, waistband, oradhesive patch). In some aspects, the transceiver 101 may remotely powerand/or communicate with the sensor to initiate and receive themeasurements (e.g., via near field communication (NFC)). However, thisis not required, and, in some alternative aspects, the transceiver 101may power and/or communicate with the sensor 100 via one or more wiredconnections. In some non-limiting aspects, the transceiver 101 may be asmartphone (e.g., an NFC-enabled smartphone). In some aspects, thetransceiver 101 may communicate information (e.g., one or more analytelevels) wirelessly (e.g., via a Bluetooth™ communication standard suchas, for example and without limitation Bluetooth Low Energy) to a handheld application running on a display device 105 (e.g., smartphone). Insome aspects, information can be downloaded from the transceiver 101through a Universal Serial Bus (USB) port. In some aspects, the analytemonitoring system 50 may include a web interface for plotting andsharing of uploaded data.

In some aspects, as illustrated in FIG. 2 , the transceiver 101 mayinclude an inductive element 103, such as, for example, a coil. In someaspects, the transceiver 101 may generate an electromagnetic wave orelectrodynamic field (e.g., by using a coil) to induce a current in aninductive element 114 of the sensor 100. In some non-limiting aspects,the sensor 100 may use the current induced in the inductive element 114to power the sensor 100. However, this is not required, and, in somealternative aspects, the sensor 100 may be powered by an internal powersource (e.g., a battery).

In some aspects, the transceiver 101 may convey data (e.g., commands) tothe sensor 100. For example, in some non-limiting aspects, thetransceiver 101 may convey data by modulating the electromagnetic wavegenerated by the inductive element 103 (e.g., by modulating the currentflowing through the inductive element 103 of the transceiver 101). Insome aspects, the sensor 100 may detect/extract the modulation in theelectromagnetic wave generated by the transceiver 101. Moreover, thetransceiver 101 may receive data (e.g., one or more sensor measurements)from the sensor 100. For example, in some non-limiting aspects, thetransceiver 101 may receive data by detecting modulations in theelectromagnetic wave generated by the sensor 100, e.g., by detectingmodulations in the current flowing through the inductive element 103 ofthe transceiver 101.

In some non-limiting aspects, as illustrated in FIG. 2 , the sensor 100may be include a sensor housing 102 (i.e., body, shell, capsule, orencasement), which may be rigid and biocompatible. The sensor 100 mayinclude an analyte indicator 106, such as, for example, a polymer graftcoated, diffused, adhered, or embedded on or in at least a portion ofthe exterior surface of the sensor housing 102. The analyte indicator106 (e.g., polymer graft) of the sensor 100 may include indicatormolecules 104 (e.g., fluorescent indicator molecules) exhibiting one ormore detectable properties (e.g., optical properties) based on thelevel, amount, or concentration of the analyte in proximity to theanalyte indicator 106.

In some aspects, as shown in FIG. 2 , the sensor 100 may include a lightsource 108 that emits excitation light 329 over a range of wavelengthsthat interact with the indicator molecules 104. The sensor 100 may alsoinclude one or more photodetectors 224, 226 (e.g., photodiodes,phototransistors, photoresistors, or other photosensitive elements). Theone or more photodetectors (e.g., photodetector 224) may be sensitive toemission light 331 (e.g., fluorescent light) emitted by the indicatormolecules 104 such that a signal generated by a photodetector (e.g.,photodetector 224) in response thereto that is indicative of the levelof emission light 331 of the indicator molecules and, thus, the amountof analyte of interest (e.g., glucose). In some non-limiting aspects,one or more of the photodetectors (e.g., photodetector 226) may besensitive to excitation light 329 that is reflected from the analyteindicator 106 as reflection light 333. In some non-limiting aspects, oneor more of the photodetectors may be covered by one or more filters(e.g., one or more bandpass filters) that allow only a certain subset ofwavelengths of light to pass through (e.g., a subset of wavelengthscorresponding to emission light 331 or a subset of wavelengthscorresponding to reflection light 333) and reflect the remainingwavelengths. In some non-limiting aspects, the sensor 100 may include atemperature transducer 670.

In some aspects, as illustrated in FIG. 2 , the sensor 100 may include asubstrate 116. In some aspects, the substrate 116 may be a circuit board(e.g., a printed circuit board (PCB) or flexible PCB) on which circuitcomponents (e.g., analog and/or digital circuit components) may bemounted or otherwise attached. However, in some alternative aspects, thesubstrate 116 may be a semiconductor substrate having circuitryfabricated therein. The circuitry may include analog and/or digitalcircuitry. Also, in some semiconductor substrate aspects, in addition tothe circuitry fabricated in the semiconductor substrate, circuitry maybe mounted or otherwise attached to the semiconductor substrate 116. Inother words, in some semiconductor substrate aspects, a portion or allof the circuitry, which may include discrete circuit elements, anintegrated circuit (e.g., an application specific integrated circuit(ASIC)) and/or other electronic components (e.g., a non-volatilememory), may be fabricated in the semiconductor substrate 116 with theremainder of the circuitry is secured to the semiconductor substrate 116and/or a core (e.g., ferrite core) for the inductive element 114. Insome aspects, the semiconductor substrate 116 and/or a core may providecommunication paths between the various secured components.

In some aspects, the one or more of the sensor housing 102, analyteindicator 106, indicator molecules 104, light source 108, photodetectors224, 226, temperature transducer 670, substrate 116, and inductiveelement 114 of sensor 100 may include some or all of the featuresdescribed in one or more of U.S. patent application Ser. No. 13/761,839,filed on Feb. 7, 2013, U.S. patent application Ser. No. 13/937,871,filed on Jul. 9, 2013, and U.S. patent application Ser. No. 13/650,016,filed on Oct. 11, 2012, all of which are incorporated by reference intheir entireties. Similarly, the structure and/or function of the sensor100 and/or transceiver 101 may be as described in one or more of U.S.patent application Ser. Nos. 13/761,839, 13/937,871, and 13/650,016.

Although in some aspects, as illustrated in FIG. 2 , the sensor 100 maybe an optical sensor, this is not required, and, in one or morealternative aspects, sensor 100 may be a different type of analytesensor, such as, for example, an electrochemical sensor, a diffusionsensor, or a pressure sensor. Also, although in some aspects, asillustrated in FIGS. 1 and 2 , the analyte sensor 100 may be a fullyimplantable sensor, this is not required. In some alternative aspects,the sensor 100 may be a transcutaneous sensor having a wired connectionto the transceiver 101. For example, in some alternative aspects, thesensor 100 may be located in or on a transcutaneous needle (e.g., at thetip thereof). In these aspects, instead of wirelessly communicatingusing inductive elements 103 and 114, the sensor 100 and transceiver 101may communicate using one or more wires connected between thetransceiver 101 and the transceiver transcutaneous needle that includesthe sensor 100. For another example, in some alternative aspects, thesensor 100 may be located in a catheter (e.g., for intravenous bloodglucose monitoring) and may communicate (wirelessly or using wires) withthe transceiver 101.

In some aspects, the sensor 100 may include a transceiver interfacedevice. In some aspects where the sensor 100 includes an antenna (e.g.,inductive element 114), the transceiver interface device may include theantenna (e.g., inductive element 114) of sensor 100. In some of thetranscutaneous aspects where there exists a wired connection between thesensor 100 and the transceiver 101, the transceiver interface device mayinclude the wired connection.

FIG. 3 is a schematic view of an external transceiver 101 according to anon-limiting embodiment. In some aspects, as shown in FIG. 3 , thetransceiver 101 may have a connector 902, such as, for example, aMicro-Universal Serial Bus (USB) connector. The connector 902 may enablea wired connection to an external device, such as a personal computer(e.g., personal computer 109) or a display device 105 (e.g., asmartphone).

The transceiver 101 may exchange data to and from the external devicethrough the connector 902 and/or may receive power through the connector902. The transceiver 101 may include a connector integrated circuit (IC)904, such as, for example, a USB-IC, which may control transmission andreceipt of data through the connector 902. The transceiver 101 may alsoinclude a charger IC 906, which may receive power via the connector 902and charge a battery 908 (e.g., lithium-polymer battery). In someaspects, the battery 908 may be rechargeable, may have a short rechargeduration, and/or may have a small size.

In some aspects, the transceiver 101 may include one or more connectorsin addition to (or as an alternative to) Micro-USB connector 904. Forexample, in one alternative embodiment, the transceiver 101 may includea spring-based connector (e.g., Pogo pin connector) in addition to (oras an alternative to) Micro-USB connector 904, and the transceiver 101may use a connection established via the spring-based connector forwired communication to a personal computer (e.g., personal computer 109)or a display device 105 (e.g., a smartphone) and/or to receive power,which may be used, for example, to charge the battery 908.

In some aspects, as shown in FIG. 3 , the transceiver 101 may have awireless communication IC 910, which enables wireless communication withan external device, such as, for example, one or more personal computers(e.g., personal computer 109) or one or more display devices 105 (e.g.,a smartphone). In one non-limiting embodiment, the wirelesscommunication IC 910 may employ one or more wireless communicationstandards to wirelessly transmit data. The wireless communicationstandard employed may be any suitable wireless communication standard,such as an ANT standard, a Bluetooth standard, or a Bluetooth Low Energy(BLE) standard (e.g., BLE 4.0). In some non-limiting aspects, thewireless communication IC 910 may be configured to wirelessly transmitdata at a frequency greater than 1 gigahertz (e.g., 2.4 or 5 GHz). Insome aspects, the wireless communication IC 910 may include an antenna(e.g., a Bluetooth antenna). In some non-limiting aspects, the antennaof the wireless communication IC 910 may be entirely contained withinthe housing (e.g., housing 206 and 220) of the transceiver 101. However,this is not required, and, in alternative aspects, all or a portion ofthe antenna of the wireless communication IC 910 may be external to thetransceiver housing.

In some aspects, the transceiver 101 may include a display interfacedevice, which may enable communication by the transceiver 101 with oneor more display devices 105. In some aspects, the display interfacedevice may include the antenna of the wireless communication IC 910and/or the connector 902. In some non-limiting aspects, the displayinterface device may additionally include the wireless communication IC910 and/or the connector IC 904.

In some aspects, as shown in FIG. 3 , the transceiver 101 may includevoltage regulators 912 and/or a voltage booster 914. The battery 908 maysupply power (via voltage booster 914) to radio-frequency identification(RFID) reader IC 916, which uses the inductive element 103 to conveyinformation (e.g., commands) to the sensor 101 and receive information(e.g., measurement information) from the sensor 100. In somenon-limiting aspects, the sensor 100 and transceiver 101 may communicateusing near field communication (NFC) (e.g., at a frequency of 13.56MHz). In the illustrated embodiment, the inductive element 103 is a flatantenna. In some non-limiting aspects, the antenna may be flexible.However, the inductive element 103 of the transceiver 101 may be in anyconfiguration that permits adequate field strength to be achieved whenbrought within adequate physical proximity to the inductive element 114of the sensor 100. In some aspects, the transceiver 101 may include apower amplifier 918 to amplify the signal to be conveyed by theinductive element 103 to the sensor 100.

In some aspects, as shown in FIG. 3 , the transceiver 101 may include aprocessor 920 and a memory 922 (e.g., Flash memory). In somenon-limiting aspects, the memory 922 may be non-volatile and/or capableof being electronically erased and/or rewritten. In some non-limitingaspects, the processor 920 may be, for example and without limitation, aperipheral interface controller (PIC) microcontroller. In some aspects,the processor 920 may control the overall operation of the transceiver101. For example, the processor 920 may control the connector IC 904 orwireless communication IC 910 to transmit data via wired or wirelesscommunication and/or control the RFID reader IC 916 to convey data viathe inductive element 103. The processor 920 may also control processingof data received via one or more of the inductive element 103, connector902, and wireless communication IC 910.

In some aspects, the transceiver 101 may include a sensor interfacedevice, which may enable communication by the transceiver 101 with asensor 100. In some aspects, the sensor interface device may include theinductive element 103. In some non-limiting aspects, the sensorinterface device may additionally include the RFID reader IC 916 and/orthe power amplifier 918. However, in some alternative aspects wherethere exists a wired connection between the sensor 100 and thetransceiver 101 (e.g., transcutaneous aspects), the sensor interfacedevice may include the wired connection.

In some aspects, as shown in FIG. 3 , the transceiver 101 may include adisplay 924 (e.g., liquid crystal display and/or one or more lightemitting diodes), which processor 920 may control to display data (e.g.,analyte levels). In some aspects, the transceiver 101 may include aspeaker 926 (e.g., a beeper) and/or a vibration motor 928, which may beactivated, for example, in the event that an alarm condition (e.g.,detection of a hypoglycemic or hyperglycemic condition) is met. Thetransceiver 101 may also include one or more additional sensors 930,which may include an accelerometer and/or a temperature sensor, that maybe used in the processing performed by the processor 920.

In some aspects, the transceiver 101 may be a body-worn transceiver thatis a rechargeable, external device worn over the sensor implantation orinsertion site. In some aspects, the transceiver 101 may be placed usingan adhesive patch or a specially designed strap or belt. In somenon-limiting aspects, the transceiver 101 may supply power to theproximate sensor 100. In some non-limiting aspects, power may besupplied to the sensor 100 through an inductive link (e.g., an inductivelink of 13.56 MHz). However, it is not required that the sensor 100receive power from the transceiver 101 (e.g., in the case of abattery-powered sensor).

In some aspects, the external transceiver 101 may receive from theanalyte sensor 100 one or more sensor measurements indicative of ananalyte level in a first medium (e.g., interstitial fluid) in proximityto the analyte indicator 106 of the analyte sensor 100. In somenon-limiting aspects, the one or more sensor measurements may include,for example and without limitation, light and/or temperaturemeasurements (e.g., one or more measurements indicative of the level ofemission light 331 from the indicator molecules 104 as measured by thephotodetector 224, one or more measurements indicative of the level ofreflection light 333 as measured by the photodetector 226, and/or one ormore temperature measurements as measured by the temperature transducer670). In some non-limiting aspects, the transceiver 101 may receive oneor more sensor measurements periodically (e.g., every 1, 2, 5, 10, or 15minutes). However, this is not required, and, in some alternativeaspects, the transceiver 101 may receive one or more sensor measurements(e.g., by swiping, hovering, or otherwise bringing the transceiver 101in proximity to the sensor 101).

In some aspects, the transceiver 101 may calculate a level (e.g.,concentration) of the analyte (e.g., glucose) in the first medium usingat least the received one or more sensor measurements. In some aspects,the transceiver 101 may additionally or alternatively calculate a levelof the analyte in a second medium (e.g., blood) using at least thereceived one or more sensor measurements and/or the calculated firstmedium analyte level. In some non-limiting aspects, the transceiver 101may calculate the second medium analyte level as M1_ROC/p₂+(1+p₃/p₂)*M1analyte, where M1_ROC is the rate of change of the first medium analytelevel, p₂ is analyte diffusion rate, p₃ is the analyte consumption rate,and M1 analyte is the calculated first medium analyte level. In someaspects, the transceiver 101 may display one or more calculated analytelevels (e.g., one or calculated second medium analyte levels) bydisplaying the analyte levels on a display of the transceiver 101 orconveying the analyte levels to a display device 105 (see FIG. 1 ). Insome aspects, the transceiver 101 may calculate one or more analytelevel trends. In some aspects, the transceiver 101 may determine whetheran alert and/or alarm condition exists, which may be signaled to theuser (e.g., through vibration by vibration motor 928 and/or an LED ofthe transceiver's display 924 and/or a user interface of a displaydevice 105). In some aspects, the transceiver 101 may store one or morecalculated analyte levels (e.g., in memory 922).

In some aspects, the transceiver 101 may convey information (e.g., oneor more of sensor data, calculated analyte levels, calculated analytelevel rates of change, alerts, alarms, and notifications) may betransmitted to a display device 105 (e.g., via Bluetooth Low Energy withAdvanced Encryption Standard (AES)-Counter CBC-MAC (CCM) encryption) fordisplay by a mobile medical application (MMA) being executed by thedisplay device 105. In some non-limiting aspects, the MMA may generatealarms, alerts, and/or notifications (in addition to or as analternative to receiving alerts, alarms, and/or notifications from thetransceiver 101). In one embodiment, the MMA may be configured toprovide push notifications.

In some aspects, the analyte monitoring system 50 may calibrate theconversion of one or more sensor measurements to one or more analytelevels. In some aspects, the calibration may be performed approximatelyperiodically (e.g., every 12 or 24 hours). In some aspects, thecalibration may be performed using one or more reference measurements(e.g., one or more self-monitoring blood glucose (SMBG) measurements),which may be entered into the analyte monitoring system 50 using theuser interface of the display device 105. In some aspects, thetransceiver 101 may receive the one or more reference measurements fromthe display device 105 and perform the calibration using the one or morereference measurements as calibration points.

In some aspects, the analyte monitoring system 50 may assess theperformance of the analyte sensor 100. In some aspects, circuitry of thetransceiver 101 (e.g., the processor 920) may perform the assessment ofthe performance of the analyte sensor 100. In some aspects, theassessment of the electronic performance may provide an objectivereference to quantify the overall sensor electronic performance. In someaspects, the assessment of the sensor electronic performance may beperformed in real time. In some aspects, the transceiver 101 may assessthe in-vivo sensor performance in real time and determine whether theperformance of the analyte sensor 100 is suitable for continuous analytemonitoring. In some aspects, the analyte monitoring system 50 maytrigger one or more of a sensor instability alert and a sensorretirement alert if the sensor electronic performance is unsuitable forcontinuous analyte monitoring.

In some aspects, the analyte monitoring system 50 may assess theperformance of the analyte sensor 100 at each sensor measurement. Insome aspects, assessing the performance of the analyte sensor 100 mayinclude calculating a metric for electronic performance (MEP). In someaspects, the MEP may reflect the real time sensor electronic performanceand may be used to determine a sensor electronic performance deficiencyand/or to trigger a sensor retirement alert. In some aspects, the MEPmay take into account measures of one or more of spikes in thecalculated analyte levels, reference channel instability, diagnosticdrift, and reference channel decreases.

In some aspects, the MEP may be the minimum value of one or moremeasures. In some aspects, the measures may include one or more of (i) aspike metric, (ii) a reference channel instability metric, (iii) adiagnostic drift metric, and (iv) a reference channel decrease metric,which are described in detail below. In some aspects, the MEP may be theminimum value of one or more measures after applying a weight to one ormore of the measures. In some non-limiting aspects, MEP may be definedas the minimum value of (i) a weighted spike metric, (ii) a weightedreference channel instability metric, (iii) a weighted diagnostic driftmetric, and (iv) a weighted reference channel decrease metric. In somenon-limiting aspects, the calculated MEP value may be passed through afilter such as, for example and without limitation, a Kalman Filter.

In some aspects, the smaller the MEP is, the worse the electronicperformance of the sensor 100 is. In some non-limiting aspects, the MEPmay always be between 0 and 1. In some non-limiting aspects, the weightsfor one or more of the spike metric, reference channel instabilitymetric, diagnostic drift metric, and reference channel decrease metricmay be specified as, for example and without limitation, 1, 1, 1, and 1,respectively. However, this is not required, and, in some alternativeaspects, the transceiver 101 may use one or more different weights. Insome aspects, these weights may be optimized for different sensorconfigurations. In some aspects, the smaller the weight for a parameteris, the more influence the parameter has on the sensor electronicperformance.

In some non-limiting aspects, the transceiver 101 may calculate MEP andthen pass the calculated value through a filter because the calculatedMEP may contain noise (e.g., noise introduced by a large temperatureswing). In some aspects, the filter may be a Kalman Filter. In somenon-limiting aspects, the transceiver 101 may use a Kalman Filtersimilar to the one described athttp://www.cs.unc.edu/˜welch/kalman/kalmanIntro.html, except that themeasurement noise R may be set equal to R₀. In some non-limitingaspects, R₀ may be equal to, for example and without limitation, 3. Insome aspects, the rest parameter update may follow a standard KalmanFilter procedure. In some aspects, the Kalman-filtered MEP may be aninitial value of 1 (i.e., the filtered MEP may always start with 1 atthe very beginning of the sensor life).

In some aspects, the transceiver 101 may store MEP values (e.g.,filtered MEP values) in an MEP buffer (e.g., in memory 922). In somenon-limiting aspects, the transceiver 101 may convey the latest MEP tothe analyte sensor 100 (e.g., for storage in a non-volatile memory ofthe sensor 100, such as an EEPROM). In some aspects, the transceiver 101may convey the most recent MEP value to the sensor 100 periodically(e.g., every 12 or 24 hours) and in case of sensor electronicperformance deficiency (see below). However, in some alternativeaspects, the MEP values may be conveyed to the sensor 100 for storage inthe sensor memory immediately regardless of the time. In some aspects,the transceiver 101 may obtain previous MEP values from the memory ofthe sensor 100 in the event MEP values in the transceiver 101 (e.g., inan MEP buffer in the memory 922) are deleted (e.g., during a transceiverreset).

In some aspects, after calculating MEP, the analyte monitoring system 50may use the calculated MEP to determine whether the electronicperformance of the analyte sensor 100 is unsuitable for continuousanalyte monitoring. In some aspects, the transceiver 101 of the analytemonitoring system 50 may calculate MEP and determine whether the sensorelectronic performance is unsuitable for continuous analyte monitoring.In some aspects, the transceiver 101 will determine that the electronicperformance of the analyte sensor 100 is deficient if MEP is below anMEP deficiency threshold. In some non-limiting aspects, the MEPdeficiency threshold may be, for example and without limitation, 0.35.In some non-limiting aspects, the MEP deficiency threshold may be withina range from 0.99 to zero, and this MEP range should be understood asdescribing and disclosing all MEP values (including all decimal orfractional MEP values) and sub-ranges within this range.

In some aspects, the transceiver 101 will determine that the analytesensor 100 should be retired if MEP is below the MEP deficiencythreshold for at least a period of time. In some non-limiting aspects,the period of time may be, for example and without limitation, 3600seconds. In some non-limiting aspects, the period of time may be withina range from one second to 10 days, and this period of time range shouldbe understood as describing and disclosing all periods of time(including all decimal or fractional seconds) and sub-ranges within thisrange. In some aspects, the transceiver 101 will only determine that theelectronic performance of the analyte sensor 100 is deficient if (i) MEPis below the MEP deficiency threshold for at least the period of timeand (ii) an initialization period (e.g., a period of, for example andwithout limitation, 1,728,000 seconds or 864,000 seconds, which mayrepresent the maximum time the analyte sensor 100 would require forhydration after implantation) has passed since the analyte sensor 100was implanted. In some non-limiting aspects, the transceiver 101 mayapproximate the sensor implant time as the time at which the transceiver101 is paired with the analyte sensor 100, which typically occursimmediately after implant.

In some aspects, the MEP values for each of the sensors may start at 1.In some non-limiting aspects, the electronic performance of the sensorsis determined to be deficient when the MEP goes below the MEP deficiencythreshold, and, for each sensor, the corresponding transceiver stopsconveying analyte level information (e.g., to a display device fordisplay) when the transceiver determines the sensor electronicperformance to be deficient.

In some aspects, if the transceiver 101 determines that the electronicperformance of the analyte sensor 100 is deficient, the analytemonitoring system 50 may consider the sensor 100 to no longer besuitable for continuous analyte monitoring, and the transceiver 101 maytrigger a sensor retirement alert, which the transceiver 101 may conveyto the display device 105. In some aspects, if the sensor 100 is nolonger be suitable for continuous analyte monitoring, the analytemonitoring system 50 may stop displaying calculated analyte levels.

FIG. 4 is a flow chart illustrating an analyte monitoring process 400according to some non-limiting aspects. In some aspects, one or moresteps of the process 400 may be performed by an analyte monitoringsystem, such as, for example, the analyte monitoring system 50. In someaspects, one or more steps of the process 400 may be performed by atransceiver, such as, for example, the transceiver 101. In somenon-limiting aspects, one or more steps of the process 400 may beperformed by a processor, such as, for example, the processor 920 of thetransceiver 101.

In some aspects, the process 400 may include a step 402 in which thetransceiver 101 receives one or more sensor measurements from the sensor100. In some non-limiting aspects, the one or more sensor measurementsmay include, for example and without limitation, one or more lightmeasurements and/or one or more temperature measurements. In someaspects, the transceiver 101 may receive the one or more sensormeasurements after conveying a command (e.g., a measurement command or aread sensor data command) to the sensor 100. However, this is notrequired, and, in some alternative aspects, the sensor 100 may controlwhen one or more sensor measurements are conveyed to the transceiver101, or the sensor 100 may continuously convey sensor measurements tothe transceiver 101. In some non-limiting aspects, the transceiver 101may receive one or more sensor measurements periodically (e.g., every 1,2, 5, 10, or 15 minutes).

In some aspects, the transceiver 101 may receive the one or more sensormeasurements using the sensor interface of the transceiver 101. In somenon-limiting aspects, the transceiver 101 may receive the one or moresensor measurements wirelessly. For example and without limitation, insome non-limiting aspects, the transceiver 101 may receive the one ormore sensor measurements by detecting modulations in an electromagneticwave generated by the sensor 100, e.g., by detecting modulations in thecurrent flowing through the inductive element 103 of the transceiver101. However, this is not required, and, in some alternative aspects,the transceiver 101 may receive the one or more sensor measurements viaa wired connection to the sensor 100.

In some aspects, the one or more sensor measurements may be associatedwith a time stamp. In some non-limiting aspects, the transceiver 101 mayreceive the time stamp from the sensor 100. In some non-limitingaspects, the received one or more sensor measurements may include thetime stamp. In some aspects, the time stamp may reflect the time atwhich the one or more sensor measurements were taken. However, it is notrequired that the transceiver 101 receive the time stamp from the sensor100. For example, in some alternative aspects, the transceiver 101 mayassign the time stamp to the one or more sensor measurements afterreceiving the one or more sensor measurements. In these aspects, thetime stamp may reflect when the transceiver 101 received the one or moresensor measurements.

In some aspects, the process 400 may include a step 404 in which thetransceiver 101 calculates a first medium analyte level (e.g., an ISFanalyte level) using the one or more sensor measurements received fromthe sensor 100. In some aspects, the first medium analyte level may be ameasurement of the amount or concentration of the analyte in the firstmedium (e.g., interstitial fluid) in proximity to the analyte sensor100. In some non-limiting aspects, calculation of the first mediumanalyte level may include, for example and without limitation, some orall of the features described in U.S. application Ser. No. 13/937,871,filed on Jul. 9, 2013, now U.S. Pat. No. 9,414,775, which isincorporated by reference herein in its entirety.

In some aspects, the process 400 may include a step 406 in which thetransceiver 101 calculates a first medium analyte level rate of change(“M1_ROC”). In some aspects, the transceiver 101 may calculate theM1_ROC using at least the first medium analyte level calculated in step404 and one or more previously calculated first medium analyte levels(e.g., one or more first medium analyte levels calculated usingpreviously received sensor measurements). In some non-limiting aspects,the transceiver 101 may calculate M1_ROC as the difference between thecalculated first medium analyte level and the most recent previouslycalculated first medium analyte level divided by the time differencebetween a time stamp for the calculated first medium analyte level and atime stamp for the most recent previously calculated first mediumanalyte level. In other words, in some non-limiting aspects, M1_ROC mayequal (M1_AL(n)−M1_AL(n−1))/(T(n)−T(n−1)), where M1_AL(n) is thecalculated first medium analyte level, M1_AL(n−1) is the most recentpreviously calculated first medium analyte level, and T(n) and T(n−1)are the time stamps. However, this is not required, and, in somealternative aspects, the transceiver 101 may calculate M1_ROC using thecalculated first medium analyte level and a plurality of the most recentpreviously calculated first medium analyte levels. In some non-limitingaspects, the plurality of the most recent previously calculated ISFanalyte levels may be, for example and without limitation, the previoustwo calculated first medium analyte levels, the previous 20 calculatedfirst medium analyte levels, or any number of previously calculated ISFanalyte levels in between (e.g., the previous 5 calculated first mediumanalyte levels). In other alternative aspects, to calculate M1_ROC, thetransceiver 101 may use the calculated first medium analyte level andthe previously calculated first medium analyte levels that werecalculated during a time period. In some non-limiting aspects, the timeperiod may be, for example and without limitation, the last one minute,the last 60 minutes, or any amount of time in between (e.g., the last 25minutes). In some aspects where the transceiver 101 uses the calculatedfirst medium analyte level and more than one previously calculated firstmedium analyte levels to calculate M1_ROC, the transceiver 101 may use,for example, linear or non-linear regression to calculate M1_ROC.

In some aspects, the process 400 may include a step 408 in which thetransceiver 101 calculates a second medium analyte level (e.g., a bloodanalyte level). In some aspects, the transceiver 101 may calculate thesecond medium analyte level by performing a lag compensation. In someaspects, the transceiver 101 may calculate the second medium analytelevel using at least the first medium analyte level and the M1_ROCcalculated in steps 404 and 406, respectively. In some aspects, thetransceiver 101 may calculate the second medium analyte level using aconversion function. In some non-limiting aspects, the transceiver 101may calculate the second medium analyte level as M1_ROC/p₂+(1+p₃/p₂)*M1analyte, where M1_ROC is the rate of change of the first medium analytelevel, p₂ is analyte diffusion rate, p₃ is the analyte consumption rate,and M1 analyte is the calculated first medium analyte level.

In some aspects, the process 400 may include a step 410 in which thetransceiver 101 performs a spike analysis to determine whether thesecond medium analyte level calculated in step 408 is a potentiallyerroneous spike. In some non-limiting aspects, the transceiver 101 maykeep track of the number of calculated second medium analyte levels thathave been determined to be potentially erroneous spikes. In somenon-limiting aspects, if the transceiver 101 determines that thecalculated second medium analyte level is a spike, the transceiver 101may increment a count of the number of calculated second medium analytelevels that have been determined to be potentially erroneous spikes. Insome non-limiting aspects, if the transceiver 101 determines that thecalculated second medium analyte level is a spike, the transceiver 101may calculate an alternative second medium analyte level. A non-limitingexample of a spike analysis process that may be performed in step 410 isdescribed below with reference to FIG. 5 .

In some aspects, the process 400 may include a step 411 in which thetransceiver 101 performs a reference channel instability analysis todetect the presence of reference channel instability. In some aspects,the reference channel instability analysis may include comparing acurrent temperature corrected reference light measurement with theprevious temperature corrected reference light measurement nearest intime to the most-recent calibration point. In some non-limiting aspects,the temperature corrected reference light measurement for the referencechannel instability analysis may be defined as equal to the referencelight measurement*(1+max(0,TempCorrectionFactor*Ref_cz/RefInstability_DefaultCz)*(temperature−37)).In some aspects, the reference light measurement may be a measurement ofthe amount of reflection light 333 received by the photodetector 226 anddigitized by an analog to digital converter of the analyte sensor 100.In some aspects, the temperature measurement may be a measurement of thesensor temperature by the temperature sensor 670 of the analyte sensor100. In some non-limiting aspects, the temperature measurement may havebeen digitized by an analog to digital converter of the analyte sensor100. In some aspects, the reference light and temperature measurementsmay be part of the one or more sensor measurements received by thetransceiver 101 in step 402. In some non-limiting aspects, theTempCorrectionFactor may be, for example and without limitation, 0.009.In some non-limiting aspects, the Ref_cz may be a temperature correctionfactor for the light source 108 of the reference channel of the sensor100. The Ref_cz may vary from one sensor to another, may be estimatedduring a sensor quality control process after manufacturing of thesensor 100 and before implantation or insertion of the sensor 100, andmay be, for example and without limitation, 0.0054122 or 0.0063641. Insome non-limiting aspects, the RefInstability_DefaultCz may be aparameter having a value of, for example and without limitation, 0.0168.

In some non-limiting aspects, the transceiver 101 may determine thatreference channel instability exists if (i) less than a threshold periodof time (e.g., 1 day) has passed between the current sensor measurementsand the most-recent calibration point and (ii) the absolute differencebetween the current temperature corrected RefOnOff_ADC with thetemperature corrected RefOnOff_ADC nearest to the most-recentcalibration point is less than or equal to an instability threshold(e.g., 0.05). In some non-limiting aspects, the transceiver 101 may onlydetermine that reference channel instability exists if the conditions(i) and (ii) are met for a number (e.g., 3) of consecutive sensormeasurements.

In some non-limiting aspects, in step 411, if reference channelinstability is detected, the transceiver 101 may perform one or more ofthe following: (i) blind the analyte monitoring system 50 by notdisplaying any calculated analyte levels, which may be erroneous, (ii)convey a sensor check communication (e.g., a sensor check alert, alarm,or notification) to the display device 105 for display of thecommunication to a user, (iii) clear a calibration buffer of thetransceiver 101 that stores one or more calibration points (e.g., one ormore reference analyte measurements received from the display device105), and (iv) have the analyte monitoring system 50 return to aninitialization phase. In some aspects, in the initialization phase, thetransceiver 101 may receive one or more sensors measurements (e.g.,periodically such as, for example and without limitation, every 2, 5, or10 minutes) and calculate second medium analyte levels, but the system50 may not display the calculated second medium analyte levels (e.g.,the transceiver 101 may not convey analyte levels to the display device105). In some aspects, in the initialization phase, the transceiver 101may receive references measurements more frequently than during a normalcalibration phase (e.g., approximately every 2 hours as opposed toapproximately every 12 hours). The transceiver 101 may use the referencemeasurements as calibration points for the calibration buffer. In someaspects, system 50 may stay in the initialization phase for a certainamount of time (e.g., 2 days) or until the transceiver 101 receives acertain number of reference measurements (e.g., 10 referencemeasurements). In some aspects, after the completion of theinitialization phase, the system 50 may proceed to the normalcalibration phase and display calculated analyte measurements.

In some aspects, the process 400 may include a step 412 in which thetransceiver 101 calculates the metric for electronic performance (MEP).In some aspects, the transceiver 101 may store the calculated MEP valuein an MEP buffer (e.g., in memory 922). In some aspects, calculating theMEP may take into account measures of one or more of spikes in thecalculated analyte levels, reference channel instability, diagnosticdrift, and reference channel decreases. A non-limiting example of aprocess that may be performed in step 412 to calculate the MEP isdescribed below with reference to FIG. 6 .

In some aspects, the process 400 may include a step 414 in which thetransceiver 101 compares the calculated MEP to the MEP deficiencythreshold (e.g., 0.35). If the comparison of the calculated MEP to theMEP deficiency threshold indicates that the sensor performance isdeficient (e.g., if the assessment of sensor performance is less thanthe deficiency threshold), the process 400 may proceed to a step 418 inwhich the transceiver 101 determines whether the sensor 100 should beretired (e.g., whether the sensor 100 has reached the end of itsfunctional life). However, if the comparison in step 414 does notindicate that the sensor performance is deficient, the process 400 mayproceed to a display step 416.

In some aspects, the process 400 may include the step 416 in which thetransceiver 101 displays a calculated second medium analyte level. Insome aspects, the second medium analyte level displayed in step 416 maybe the second medium analyte level calculated in step 408. However, inaspects in which the spike analysis step 410 calculates an alternativesecond medium level if a spike is detected, the second medium analytelevel displayed in step 416 may be (a) the second medium analyte levelcalculated in step 408 if no spike is detected in step 410 or (b) thealternative second medium analyte level calculated in step 410 if aspike is detected in step 410. In some aspects, in step 416, thetransceiver 101 may display the analyte level on the display 924. Insome aspects, in step 416, the transceiver 101 may additionally oralternatively display the second medium analyte level by conveying it tothe display device 105, and the display device 105 may additionally oralternatively display the calculated second medium analyte level.

In some aspects, the process 400 may include the step 418 in which thetransceiver 101 determines whether the sensor 100 should be retired(e.g., whether the sensor 100 has reached the end of its functionallife). In some aspects, the transceiver 101 will determine that theanalyte sensor 100 should be retired if MEP is below the MEP deficiencythreshold for at least a period of time (e.g., 3600 seconds). In someaspects, the transceiver 101 will only determine that the electronicperformance of the analyte sensor 100 is deficient if (i) MEP is belowthe MEP deficiency threshold for at least the period of time and (ii) aninitialization period (e.g., 1,728,000 seconds or 864,000 seconds) haspassed since the analyte sensor 100 was implanted. In some aspects, ifthe transceiver 101 determines that the sensor 100 need not be retired,the process 400 may proceed from the step 418 to the display step 416.In some aspects, if the transceiver 101 determines that the sensor 100should be retired, the process 400 may proceed from the step 418 to asensor retirement step 420.

In some aspects, in the sensor retirement step 420, the transceiver 101may display a sensor retirement indication. In some aspects, thetransceiver 101 may display the sensor retirement indication byconveying a sensor retirement communication (e.g., a sensor retirementalarm, alert, or notification) to the display device 105. In somenon-limiting aspects, the transceiver 101 may additionally oralternatively blind the sensor output (e.g., stop conveying calculatedsecond medium analyte levels to the display device 105 for display). Insome aspects, in response to receiving the sensor retirementcommunication, the display device 105 may display an indication that thesensor needs to be replaced and/or that analyte levels will not bedisplayed until after the sensor 100 is replaced.

FIG. 5 is a flow chart illustrating a spike analysis process 500, whichmay be performed during the spike analysis step 410 of the analytemonitoring process 400 illustrated in FIG. 4 . In some aspects, thetransceiver 101 may perform one or more steps of the spike analysisprocess 500. In some non-limiting aspects, the processor 920 of thetransceiver 101 may perform one or more steps of the spike analysisprocess 500.

In some aspects, the spike analysis process 500 may include a step 502in which the transceiver 101 determines whether one or more prescreeningcriteria are met. In some non-limiting aspects, the prescreeningcriteria may include one or more of: (i) that at least three calculatedsecond medium analyte levels are stored in the transceiver 101 (e.g., inan analyte level buffer of memory 922), (ii) that one or more calculatedanalyte levels (e.g., the calculated first medium analyte level and thecalculated second medium analyte level) are valid, and (iii) that thecalculated that the transceiver 101 has not performed a calibrationrecently (e.g., since the calculating the previous second medium analytelevel). In some non-limiting aspects, one or more calculated analytelevels may be determined to be valid if the calculated analyte levelsare between 40 and 400 mg/dL. In some aspects, if the prescreeningcriteria are met, the spike analysis process 500 may proceed to a spikedetection step 504.

In some aspects, in the spike detection step 504, the transceiver 101may determine whether the calculated second medium analyte level (e.g.,the second medium analyte level calculated in step 408 of the process400 illustrated in FIG. 4 ) is a spike. In some aspects, determiningwhether a calculated second medium analyte level is a spike may includeone or more of (i) determining whether the first medium analyte level ischanging faster than a first medium analyte level rate of changethreshold (“M1_ROC threshold”), (ii) determining whether the secondmedium analyte level is changing faster than a second medium analytelevel rate of change threshold (“M2_ROC threshold”), (iii) determiningwhether a difference between the first medium analyte level rate ofchange and the previous first medium analyte level rate of change isgreater than a first medium analyte level rate of change differencethreshold (“M1_ROC difference threshold”), and (iv) determining whethera difference between the second medium analyte level rate of change andthe previous second medium analyte level rate of change is greater thana second medium analyte level rate of change difference threshold(“M2_ROC difference threshold”). In some non-limiting aspects, thetransceiver 101 may determine that the second medium analyte level is aspike only if all four of the thresholds are exceeded. However, this isnot required, and, in some alternative aspects, the transceiver 101 maydetermine that the second medium analyte level is a spike if fewer thanall of the thresholds are exceeded (e.g., only if three or morethresholds are exceeded, only if two more thresholds are exceeded, or ifany threshold is exceeded).

In some aspects, determining whether the first medium analyte level ischanging faster than a first medium analyte level rate of changethreshold in step 504 may include comparing the M1_ROC (e.g., the M1_ROCcalculated in step 406 and used to calculate the second medium analytelevel in step 408 of the process 400 illustrated in FIG. 4 ) to theM1_ROC threshold. In some aspects, determining whether the first mediumanalyte level is changing faster than the M1_ROC threshold may includecomparing the absolute value of M1_ROC to the M1_ROC threshold. In somenon-limiting aspects, the M1_ROC threshold may be, for example andwithout limitation, 1.5 mg/dL/min.

In some aspects, determining whether the second medium analyte level ischanging faster than the M2_ROC threshold in step 504 may includecalculating the rate of change of the second medium analyte level(“M2_ROC”). In some non-limiting aspects, the transceiver 101 maycalculate M2_ROC as the difference between the calculated second mediumanalyte level and most recent previously calculated second mediumanalyte level divided by the time difference between a time stamp forthe calculated second medium analyte level and a time stamp for the mostrecent previously calculated second medium analyte level. In otherwords, in some non-limiting aspects, M2_ROC may equal(M2_AL(n)−M2_AL(n−1))/(T(n)−T(n−1)), where M2_AL(n) is the calculatedsecond medium analyte level, M2_AL(n−1) is the most recent previouslycalculated second medium analyte level, and T(n) and T(n−1) are the timestamps. However, this is not required, and, in some alternative aspects,the transceiver 101 may calculate M2_ROC using the calculated secondmedium analyte level and a plurality of the most recent previouslycalculated second medium analyte levels.

In some aspects, determining whether the second medium analyte level ischanging faster than the M2_ROC threshold in step 504 may includecomparing M2_ROC to the M2_ROC threshold. In some aspects, determiningwhether the second medium analyte level is changing faster than theM2_ROC threshold in step 504 may include comparing the absolute value ofM2_ROC to the M2_ROC threshold. In some non-limiting aspects, the M2_ROCthreshold may be, for example and without limitation, 4 mg/dL/min.

In some aspects, determining whether a difference between the currentM1_ROC and the previous M1_ROC is greater than the M1_ROC differencethreshold in step 504 may include calculating the difference between thecurrent M1_ROC (i.e., M1_ROC(n)) and the previous M1_ROC (i.e.,M1_ROC(n−1)). In some aspects, determining whether a difference betweenthe current M1_ROC and the previous M1_ROC is greater than the M1_ROCdifference threshold in step 504 may include comparing the differencebetween the current M1_ROC and the previous M1_ROC to the M1_ROCdifference threshold. In some aspects, determining whether a differencebetween the first medium analyte level rate of change and the previousfirst medium analyte level rate of change is greater than the M1_ROCdifference threshold may include comparing the absolute value of thedifference between the current M1_ROC and the previous M1_ROC to theM1_ROC difference threshold. In some non-limiting aspects, the M1_ROCdifference threshold may be, for example and without limitation, 2mg/dL/min.

In some aspects, determining whether a difference between the currentM2_ROC and the previous M2_ROC is greater than the M2_ROC differencethreshold in step 504 may include calculating the difference between thecurrent M2_ROC (i.e., M2_ROC(n)) and the previous M2_ROC (i.e.,M2_ROC(n−1)). In some aspects, determining whether a difference betweenthe current M2_ROC and the previous M2_ROC is greater than the M2_ROCdifference threshold in step 504 may include comparing the differencebetween the current M2_ROC and the previous M2_ROC to the M2_ROCdifference threshold. In some aspects, determining whether a differencebetween the current M2_ROC and the previous M2_ROC is greater than theM2_ROC difference threshold may include comparing the absolute value ofthe difference between the current M2_ROC and the previous M2_ROC to theM2_ROC difference threshold. In some non-limiting aspects, the M2_ROCdifference threshold may be, for example and without limitation, 4mg/dL/min.

In some aspects, the spike analysis process 500 may include a step 506in which the transceiver 101 determines whether the current calculatedsecond medium analyte level (i.e., M2_AL(n)) was determined to be spikein step 504. In some aspects, if the current calculated second mediumanalyte level was determined to be a spike, the process 500 may proceedfrom step 506 to one or more of steps 508, 510, and 512. In someaspects, if the current calculated second medium analyte level was notdetermined to be a spike, the process 500 may proceed from the step 506to a step 514.

In some aspects, the spike analysis process 500 may include a step 508in which the transceiver 101 increments a count of the number ofcalculated second medium analyte levels that have been determined to bespikes. In some aspects, the spike count may be stored in a memory(e.g., memory 922) of the transceiver 101.

In some aspects, the spike analysis process 500 may include a step 510in which the transceiver 101 calculates an alternative second mediumanalyte level. In some aspects, the transceiver 101 may display thealternative second medium analyte level (e.g., convey the alternativesecond medium analyte level to the display device 105) instead of thesecond medium analyte level calculated in step 408 and determined to bea spike in step 504. In some aspects, calculating the alternative secondmedium analyte level may include calculating one or more of (i) apredicted second medium analyte level, (ii) an M2_ROC threshold-limitedsecond medium analyte level, and (iii) a dynamic Kalman filtered secondmedium analyte value per noise variance. In some non-limiting aspects,the predicted second medium analyte level may be calculated using atleast the previous calculated second medium analyte level and theprevious M2_ROC. For example and without limitation, in one non-limitingembodiment, predicted M2_AL(n)=M2_AL(n−1)+(M2_ROC(n−1)*(T(n)−T(n−1))),where predicted M2_AL(n) is the predicted second medium analyte level,M2_AL(n−1) is the previous calculated second medium analyte level,M2_ROC(n−1) is the previous second medium analyte level rate of change,and T(n) and T(n−1) are the time stamps for the current and previoussecond medium analyte levels, respectively. In some non-limitingaspects, the M2_ROC threshold-limited second medium analyte level may becalculated using at least the previous calculated second medium analytelevel and the M2_ROC threshold. For example and without limitation, inone non-limiting embodiment, threshold-limitedM2_AL(n)=M2_AL(n−1)+(M2_ROC threshold*(T(n)−T(n−1))) if M2_ROC(n) ispositive, and threshold-limited M2_AL(n)=M2_AL(n−1)−(M2_ROCthreshold*(T(n)−T(n−1))) if M2_ROC(n) is negative, wherethreshold-limited M2_AL(n) is the M2_ROC threshold-limited second mediumanalyte level, M2_AL(n−1) is the previous calculated second mediumanalyte level, M2_ROC threshold is the second medium analyte level rateof change threshold, T(n) and T(n−1) are the time stamps for the currentand previous second medium analyte levels, respectively, and M2_ROC(n)is the current second medium analyte level rate of change. In somenon-limiting aspects, the alternative second medium analyte level may bethe average of two or more of (i) the predicted second medium analytelevel, (ii) the M2_ROC threshold-limited second medium analyte level,and (iii) the dynamic Kalman filtered second medium analyte value pernoise variance.

In some aspects, the spike analysis process 500 may include a step 512in which the transceiver 101 stores the alternative second mediumanalyte level in the transceiver 101 (e.g., in the analyte level bufferof memory 922). In some non-limiting aspects, the transceiver 101 mayadditionally store an indication that stored value is an alternativevalue. In some aspects, the transceiver 101 may store both the secondmedium analyte level calculated in step 408 of process 400 and thealternative second medium analyte level calculated in step 510. In somealternative aspects, the transceiver 101 may store the alternativesecond medium analyte level in place of the second medium analyte level,which was determined to be a spike in step 504. In some aspects, theprocess 500 may proceed from steps 508, 510, and 512 to the step 514.

In some aspects, in step 514, the transceiver 101 may check whether theprevious calculated second medium analyte level (i.e., M2_AL(n)) wasdetermined to be spike (e.g., in the previous iteration of step 504). Insome aspects, if the previous calculated second medium analyte level wasdetermined to be a spike, the process 500 may proceed from step 514 toone or more of steps 516, 518, 520, and 522.

In some aspects, the spike analysis process 500 may include a step 516in which the transceiver 101 performs a retrospective spike crossvalidation that uses at least the current second medium analyte level todetermine whether a previous second medium analyte level that wasdetermined to be a spike truly was a spike. In some aspects, in step516, the transceiver 101 may check whether the absolute differencebetween (a) the average of the current second medium analyte level andthe second medium analyte level before the previous second mediumanalyte level and (b) the previous second medium analyte level (“thefirst absolute difference”) is greater than or equal to a firstthreshold. In some aspects, the transceiver 101 may additionally oralternatively check whether the absolute difference between (a) theaverage of the current first medium analyte level and the first mediumanalyte level before the previous first medium analyte level and (b) theprevious first medium analyte level (“the second absolute difference”)is greater than or equal to a second threshold. In some non-limitingaspects, the first and second thresholds may be, for example and withoutlimitation, 10 mg/dL and 8.5 mg/dL, respectively. In some aspects, thetransceiver 101 may determine that the previous second medium analytelevel was truly a spike if any of the first absolute difference isgreater than or equal to the first threshold, the second absolutedifference is greater than or equal to the second threshold, or both. Insome non-limiting aspects, the transceiver 101 may determine that theprevious second medium analyte level was not truly a spike if the firstabsolute difference is less than the first threshold and the secondabsolute difference is less than the second threshold.

In some aspects, the spike analysis process 500 may include a step 518in which the transceiver 101 determines whether the previous secondmedium analyte level (i.e., M2_AL(n−1)) was determined to be a truespike in step 516. In some aspects, if the previous second mediumanalyte level was determined to not be a true spike, the process 500 mayproceed from step 518 to a step 520 in which the transceiver 101 mayupdate the analyte level buffer (e.g., in the of memory 922) by deletingthe previous alternative second medium analyte level (e.g., thealternative M2_AL(n−1) previously calculated in step 510) and leavingthe previous second medium analyte level (e.g., the M2_AL(n−1)previously calculated in step 408). In some alternative aspects, theprocess 500 may not include the step 520, and, if the previous secondmedium analyte level was determined to not be a true spike, the process500 may do nothing (i.e., proceed directly from step 518 to “end” inFIG. 5 ). In some aspects, if the previous second medium analyte levelwas determined to be a true spike, the process 500 may proceed from step518 to a step 522 in which the transceiver 101 may update the analytelevel buffer (e.g., in the of memory 922) by deleting the previoussecond medium analyte level (e.g., the M2_AL(n−1) previously calculatedin step 408) and leaving the previous alternative second medium analytelevel (e.g., the alternative M2_AL(n−1) previously calculated in step510).

FIG. 6 is a flow chart illustrating an MEP calculation process 600,which may be performed during the MEP calculation step 412 of theanalyte monitoring process 400 illustrated in FIG. 4 . In some aspects,the transceiver 101 may perform one or more steps of the MEP calculationprocess 600. In some non-limiting aspects, the processor 920 of thetransceiver 101 may perform one or more steps of the MEP calculationprocess 600.

In some aspects, the MEP calculation process 600 may include a step 602in which the transceiver 101 calculates a spike metric. In some aspects,the spike metric may quantify the noise level in the calculated analytecalculations, which may be displayed by the display device 105. In somenon-limiting aspects, the spike metric may range, for example andwithout limitation, from 0 to 1 with 1 being its default value andrepresenting no noise.

In some aspects, the transceiver 101 may calculate the spike metricbased on the number of detected spikes in the calculated analyte levels.In some aspects, the spikes may be detected in the spike analysis step410 of the process 400 illustrated in FIG. 4 . In some non-limitingaspects, the spikes may be detected in the spike detection step 504 ofthe spike analysis process 500 illustrated in FIG. 5 , which may beperformed during the spike analysis step 410 of the process 400illustrated in FIG. 4 . In some aspects, the number of detected spikesmay be tracked using the spike count incremented in step 508 each time aspike is detected.

In some non-limiting aspects, the transceiver 101 may calculate thespike metric as the maximum value of (a) zero and (b) the number ofcalculated second medium analyte levels minus the spike metric weightmultiplied by the number of detected spikes in the calculated secondmedium analyte levels divided by the number of calculated second mediumanalyte levels. In some non-limiting aspects, the transceiver 101 mayuse the number of MEP values that the transceiver 101 has calculated(e.g., in step 412) and stored in a memory of the transceiver 101 (i.e.,the MEP buffer size) as indicative of the number of calculated secondmedium analyte levels. However, this is not required, and, in somealternative aspects, the transceiver 101 may use a different value(e.g., the number of calculated second medium analyte levels stored inan analyte level buffer of the transceiver 101 (“analyte level buffersize”)) as indicative of the number of calculated second medium analytelevels. In some aspects, the spike metric may be calculated as max(0,(MEP buffer size−spike_metric_weight*number of detected spikes)/MEPbuffer size). In some alternative aspects, the spike metric may becalculated as max(0, (analyte level buffersize−spike_metric_weight*number of detected spikes)/analyte level buffersize). In some non-limiting aspects, the spike_metric_weight may be, forexample and without limitation, 2.25.

In some aspects, the MEP calculation process 600 may include a step 604in which the transceiver 101 calculates a reference channel instabilitymetric. In some aspects, the reference channel instability metric mayquantify the stability of the reference channel. In some non-limitingaspects, the reference channel instability metric may range, for exampleand without limitation, from 0 to 1 with 1 being its default value andrepresenting perfect reference channel stability.

In some non-limiting aspects, in step 604, if the transceiver 101 doesnot determine that reference channel instability exists in step 411 ofthe process 400, the transceiver 101 may calculate the current referencechannel instability metric as equal to the previous reference channelinstability metric. In other words, in some aspects, if the transceiver101 has not determined that reference channel instability exists, thereference channel instability metric may not change. In somenon-limiting aspects, in step 604, if the transceiver 101 determinesthat reference channel instability exists in step 411, the transceiver101 may calculate the current reference channel instability metric asequal to min(1, max(0, previous reference channel instabilitymetric−(1/instability scaler))). In some non-limiting aspects, theinstability scaler may be, for example and without limitation, 76.

In some aspects, the MEP calculation process 600 may include a step 606in which the transceiver 101 calculates a diagnostic drift metric. Insome aspects, the diagnostic drift metric may quantify the extent towhich a diagnostic measurement has drifted from its factory value (i.e.,the diagnostic measurement value during a sensor quality control processafter manufacturing of the sensor 100 and before implantation orinsertion of the sensor 100). In some non-limiting aspects, thediagnostic measurement may be, for example and without limitation, theelectronic offset of the measurement system (e.g., a measurement of theoutput of a transimpedance amplifier of the sensor 100 with nophotodetector connected to the transimpedance amplifier). In somenon-limiting aspects, the diagnostic drift metric may range from 0 to 1with 1 being its default value and representing that no diagnostic drifthas occurred. In some non-limiting aspects, the transceiver 101 maycalculate the diagnostic drift metric as equal to min(1, max(0,(maximumDriftThreshold−driftvalue)/(maximumDriftThreshold−driftThreshold))), where the drift valueis equal to the absolute value of (diagnosticmeasurement−factoryDiagnostic), and the factoryDiagnostic value isfactory value of the diagnostic measurement. In some non-limitingaspects, the maximumDriftThreshold may be, for example and withoutlimitation, 10. In some non-limiting aspects, the driftThreshold may be,for example and without limitation, 4.

In some aspects, the MEP calculation process 600 may include a step 608in which the transceiver 101 calculates a reference channel decreasemetric. In some aspects, the reference channel decrease metric mayquantify the extent to which the signal in the reference channel of thesensor 100 has decreased. In some non-limiting aspects, a decrease inthe signal in the reference channel may reflect a dimming of theexcitation light 329 emitted by light source 108. In some non-limitingaspects, the reference channel decrease metric may ranges from 0 to 1with 1 being its default value and representing excitation light 329 atits normal state. In some non-limiting aspects, the transceiver 101 maycalculate the reference channel decrease metric as equal to min(1,max(0, (mean temperature corrected reference lightmeasurement/POSTGRAFT_REF_s0_37−FILT_lowRefZeroValue)/(FILT_lowRefOneValue−FILT_lowRefZeroValue))).In some non-limiting aspects, the POSTGRAFT_REF_s0_37 may be a referencevalue in nanoamps for the unbound glucose indicator at 37°. ThePOSTGRAFT_REF_s0_37 may vary from one sensor to another. ThePOSTGRAFT_REF_s0_37 may be, for example and without limitation, 36.2422nA. In some non-limiting aspects, the FILT_lowRefZeroValue may be areference value in nanoamps at which the reference channel decreasemetric goes to zero. The FILT_lowRefZeroValue may be, for example andwithout limitation, 0.25. In some non-limiting aspects, theFILT_lowRefOneValue may be a reference value in nanoamps at which thereference channel decrease metric drops below 1. The FILT_lowRefOneValuemay be, for example and without limitation, 0.7. In some aspects, themean temperature corrected reference light measurement may be theaverage value of the temperature corrected reference light measurementsstored in the transceiver 101 (e.g., in a physical value circular bufferof the memory 922). In some aspects, the temperature corrected referencelight measurements may be equal to (1+Ref_cz*(temperature−37))*referencelight measurement. In some non-limiting aspects, the Ref_cz may be atemperature correction factor for the light source 108 of the referencechannel of the sensor 100. The Ref_cz may vary from one sensor toanother, may be estimated during a sensor quality control process aftermanufacturing of the sensor 100 and before implantation or insertion ofthe sensor 100, and may be, for example and without limitation,0.0054122 or 0.0063641. In some aspects, the reference light measurementmay be a measurement of the amount of reflection light 333 received bythe photodetector 226 and digitized by an analog to digital converter ofthe analyte sensor 100. In some aspects, the temperature measurement maybe a measurement of the sensor temperature by the temperature sensor 670of the analyte sensor 100. In some non-limiting aspects, the temperaturemeasurement may have been digitized by an analog to digital converter ofthe analyte sensor 100. In some aspects, the reference light andtemperature measurements may be part of the one or more sensormeasurements received by the transceiver 101 in step 402.

In some aspects, the MEP calculation process 600 may include a step 610in which the transceiver 101 applies weights to one or more of the spikemetric, reference channel instability metric, diagnostic drift metric,and reference channel decrease metric calculated in steps 602, 604, 606,and 608, respectively. In some non-limiting aspects, the weights for oneor more of the spike metric, reference channel instability metric,diagnostic drift metric, and reference channel decrease metric may bespecified as, for example and without limitation, 1, 1, 1, and 1,respectively. However, this is not required, and, in some alternativeaspects, the transceiver 101 may use one or more different weights. Insome aspects, these weights may be optimized for different sensorconfigurations. In some aspects, the smaller the weight for a parameteris, the more influence the parameter has on the sensor electronicperformance.

In some aspects, the MEP calculation process 600 may include a step 612in which the transceiver 101 calculates a raw MEP value using one ormore of the spike metric, reference channel instability metric,diagnostic drift metric, and reference channel decrease metric. In somenon-limiting aspects, the raw MEP value may be the minimum value of twoor more of the calculated metrics. In some non-limiting aspects, the rawMEP value may be the minimum value of three or more of the calculatedmetrics. In some non-limiting aspects, the raw MEP value may be theminimum value of the spike metric, reference channel instability metric,diagnostic drift metric, and reference channel decrease metric.

In some aspects, the MEP calculation process 600 may include a step 614in which the transceiver 101 passes the calculated MEP value through afilter because the calculated MEP value may contain noise (e.g., noiseintroduced by errors in calibration points). In some aspects, the filtermay be a Kalman Filter. In some non-limiting aspects, the transceiver101 may use a Kalman Filter similar to the one described athttp://www.cs.unc.edu/˜welch/kalman/kalmanIntro.html, except that themeasurement noise R may be set equal to R₀. In some non-limitingaspects, R₀ may be equal to, for example and without limitation, 3. Insome aspects, the rest parameter update may follow a standard KalmanFilter procedure. In some aspects, the Kalman-filtered MEP may be aninitial value of 1 (i.e., the filtered MEP may always start with 1 atthe very beginning of the sensor life).

In some aspects, the MEP calculation process 600 may include a step 616in which the transceiver 101 stores the MEP value (e.g., the filteredMEP value) in an MEP buffer of the transceiver 101 (e.g., in memory922).

In some aspects, the analyte monitoring system 50 may predict the end ofthe functional life of an implanted analyte sensor 100. The manner inwhich an analyte sensor 100 implanted (fully or partially) in the bodyperforms electronically may vary widely from sensor to sensor (and/orbody to body). That is, a sensor's electronic performance over time mayvary on a sensor by sensor basis (and/or on a patient by patient basis).Accordingly, in some aspects, the analyte monitoring system 50 mayutilize information on the electronic performance of the analyte sensor100 in order to predict the end of the functional life of analyte sensor100.

In some aspects, the transceiver 101 of the analyte monitoring system 50may predict the end of the functional life of the implanted analytesensor 100. In other words, in some aspects, the transceiver 101 maypredict the number the number of days remaining before the sensorperformance is determined to be deficient for use in continuous analytemonitoring. In some aspects, the transceiver 101 may use the assessmentof sensor electronic performance, which may be based on the metric forreal time assessment of sensor electronic performance (MEP), to predictthe sensor end of life (EOL). In some aspects, the transceiver 101 mayuse time since the sensor 100 was implanted (in addition to or as analternative to the assessment of sensor electronic performance) topredict the sensor EOL.

In some aspects, the transceiver 101 may associate one or more sensorelectronic performance assessment thresholds and/or one or more timesince implant thresholds with one or more predictions of time remainingbefore sensor EOL. In some aspects, if the transceiver 101 calculates anMEP value less than a sensor electronic performance assessment thresholdor if the time since implant exceeds a time since implant threshold, thetransceiver 101 may predict the associated amount of time remainingbefore sensor EOL. In some aspects, the transceiver 101 may convey thepredicted amount of time remaining before sensor EOL to the displaydevice 105 (e.g., as a notification, alert, or alarm), and the displaydevice 105 may display an appropriate indication of the predicted amountof time remaining before sensor EOL. See, e.g., FIGS. 7A-21 and thedescription thereof in U.S. patent application Ser. No. 15/786,954,filed on Oct. 18, 2017, which is incorporated by reference in itsentirety.

In some aspects, the transceiver 101 may use one or more previous MEPvalues to train an autoregressive (AR) model. In some non-limitingaspects, the transceiver 101 may begin using MEP values to train the ARmodel after a period of time (e.g., 20 days) has passed since sensorimplant. As noted above, in some non-limiting aspects, the transceiver101 may approximate the sensor implant time as the time at which thetransceiver 101 is paired with the analyte sensor 100, which typicallyoccurs immediately after implant. In some aspects, the transceiver 101may use the AR model to predict one or more future MEP values. If,within a prediction time period (e.g., one, two, three, or four weeks),the predicted MEP values cross an MEP deficiency threshold (e.g., 0.35)at which sensor electronic performance is determined to be deficient(e.g., unsuitable for the continuous analyte monitoring), thetransceiver 101 may use the time (e.g., day or hour) at which thepredicted MEP crosses the MEP deficiency threshold as the predicted timeof sensor EOL. See, e.g., FIGS. 22-23 and the description thereof inU.S. patent application Ser. No. 15/786,954, filed on Oct. 18, 2017,which is incorporated by reference in its entirety.

In some aspects, the transceiver 101 may begin predicting the sensor EOLafter a particular time has passed since the sensor 100 was implanted(e.g., 60 days since implant). In some aspects, the transceiver 101 maypredict sensor EOL periodically (e.g., after each calibration, daily, orevery other day). In some aspects, the frequency at which sensor EOL ispredicted may vary over time (e.g., the transceiver 101 may predictsensor EOL more frequently the closer the sensor gets to EOL). In someaspects, each time the transceiver 101 predicts sensor EOL (or each timethe predicted time of sensor EOL is different than the previouspredicted time of sensor EOL), the transceiver 101 may convey thepredicted time of sensor EOL to the display device 105 (e.g., as anotification, alert, or alarm), and the display device 105 may displayan appropriate indication of the predicted time of sensor EOL.

Aspects of the present invention have been fully described above withreference to the drawing figures. Although the invention has beendescribed based upon these preferred aspects, it would be apparent tothose of skill in the art that certain modifications, variations, andalternative constructions could be made to the described aspects withinthe spirit and scope of the invention. For instance, although aspects ofthe invention have been described above with respect to assessing sensorperformance in an analyte monitoring system, in some alternativeaspects, the assessing sensor performance of the present invention maybe applied to different devices (e.g., temperature sensors, insulinpumps, or pacemakers) in different systems (e.g., temperature monitoringsystems, insulin delivery systems, or cardiac contraction controlsystems). Also, although examples of particular parameters, thresholds,and time periods used in the sensor performance assessment have beendescribed above, the parameters, thresholds, and time periods may varyfrom one embodiment to the next, and different parameters, thresholds,and time periods may be used for different sensors and/or systemconfigurations.

In addition, although in some aspects the transceiver 101 of the analytemonitoring system 50 performs the sensor performance assessment, this isnot required. In some alternative aspects, portions of or all of thesensor performance assessment may be performed by one or more of theanalyte sensor 100 and display device 105.

Moreover, although some aspects have been described as using an ARmodel, this is not required. Some alternative aspects may use adifferent model, such as, for example and without limitation, linearregression, multivariate adaptive regression splines (MARS), exponentialdecay model, AR model with regularization, a fitted linear model, anon-linear (polynomial) model, or other predictive model defined bystatically or analytically derived expressions.

What is claimed is:
 1. An analyte monitoring system comprising: ananalyte sensor including an indicator having one or more detectableproperties indicative of an amount or concentration of an analyte in afirst medium in proximity to the indicator; and a transceiver configuredto: receive one or more sensor measurements from the analyte sensor,wherein the one or more sensor measurements comprise at least areference measurement and a signal measurement; calculate an analytelevel using at least the signal measurement; detect whether referencechannel instability is present using at least the reference measurement;if reference channel instability is not detected, display the calculatedanalyte level; if reference channel instability is detected, blind theanalyte monitoring system by not displaying the calculated analytelevel.
 2. The analyte monitoring system of claim 1, wherein: theindicator comprises indicator molecules; the analyte sensor furthercomprises (i) a light source configured to emit excitation light thatinteracts with the indicator molecules, (ii) one or more photodetectorssensitive to emission light emitted by the indicator molecules, and(iii) one or more photodetectors sensitive to excitation light reflectedfrom the indicator as reflection light; the signal measurement isindicative of a level of the emission light; and the referencemeasurement is indicative of a level of the reflection light.
 3. Theanalyte monitoring system of claim 1, wherein the transceiver, indetecting whether reference channel instability is present, isconfigured to compare a difference between the reference measurement anda previous reference measurement to an instability threshold.
 4. Theanalyte monitoring system of claim 3, wherein the one or more sensormeasurements further comprise a temperature measurement, and thetransceiver is further configured to temperature correct the referencemeasurement using at least the temperature measurement.
 5. The analytemonitoring system of claim 4, wherein the transceiver, in detectingwhether reference channel instability is present, is configured tocompare a difference between the temperature corrected referencemeasurement and a previous temperature corrected reference measurementto an instability threshold.
 6. The analyte monitoring system of claim5, wherein the transceiver, in detecting whether reference channelinstability is present, is configured to compare a difference between atime of the temperature corrected reference measurement and a time ofthe previous temperature corrected reference measurement to a timethreshold.
 7. The analyte monitoring system of claim 1, furthercomprising a display device, wherein: the transceiver is configured todisplay the calculated analyte level by conveying the calculated analytelevel; the display device is configured to receive and display thecalculated analyte level; and the transceiver, in blinding the analytemonitoring system, is configured to not convey the calculated analytelevel to the display device.
 8. The analyte monitoring system of claim1, wherein the transceiver is further configured to, if referencechannel instability is detected, convey a sensor check communication tothe display device.
 9. The analyte monitoring system of claim 1, whereinthe transceiver comprises a calibration buffer that stores one or morecalibration points, and the transceiver is further configured to, ifreference channel instability is detected, clear the calibration buffer.10. The analyte monitoring system of claim 1, wherein: the transceiveris further configured to, if reference channel instability is detected,transition the analyte monitoring system from a normal calibration phaseto an initialization phase; in the initialization phase, the transceiveris configured to store calibration points more frequently than duringthe normal calibration phase; and in the initialization phase, thetransceiver is configured to calculate but not display analyte levels.11. A method comprising: receiving one or more sensor measurements froman analyte sensor of an analyte monitoring system, wherein the analytesensor includes an indicator having one or more detectable propertiesindicative of an amount or concentration of an analyte in a medium inproximity to the indicator, and the one or more sensor measurementscomprise at least a reference measurement and a signal measurement;calculating an analyte level using at least the signal measurement;detecting that reference channel instability is present using at leastthe reference measurement; and if reference channel instability isdetected, blinding the analyte monitoring system by not displaying thecalculated analyte level.
 12. The method of claim 11, wherein: theindicator comprises indicator molecules; the analyte sensor furthercomprises (i) a light source configured to emit excitation light thatinteracts with the indicator molecules, (ii) one or more photodetectorssensitive to emission light emitted by the indicator molecules, and(iii) one or more photodetectors sensitive to excitation light reflectedfrom the indicator as reflection light; the signal measurement isindicative of a level of the emission light; and the referencemeasurement is indicative of a level of the reflection light.
 13. Themethod of claim 11, wherein detecting that the reference channelinstability is present comprises comparing a difference between thereference measurement and a previous reference measurement to aninstability threshold.
 14. The method of claim 13, wherein the one ormore sensor measurements further comprise a temperature measurement, andthe method further comprises temperature correcting the referencemeasurement using at least the temperature measurement.
 15. The methodof claim 14, wherein detecting that reference channel instability ispresent comprises comparing a difference between the temperaturecorrected reference measurement and a previous temperature correctedreference measurement to an instability threshold.
 16. The method ofclaim 15, wherein detecting that reference channel instability ispresent comprises comparing a difference between a time of thetemperature corrected reference measurement and a time of the previoustemperature corrected reference measurement to a time threshold.
 17. Themethod of claim 11, wherein the analyte monitoring system furthercomprises a display device, and blinding the analyte monitoring systemcomprises to not conveying the calculated analyte level.
 18. The methodof claim 17, further comprising, if reference channel instability isdetected, conveying a sensor check communication to the display device.19. The method of claim 11, wherein the analyte monitoring systemcomprises a calibration buffer that stores one or more calibrationpoints, and the method further comprises, if reference channelinstability is detected, clearing the calibration buffer.
 20. The methodof claim 11, further comprising, if reference channel instability isdetected, transitioning the analyte monitoring system from a normalcalibration phase to an initialization phase, wherein: in theinitialization phase, the analyte monitoring system is configured tostore calibration points more frequently than during the normalcalibration phase; and in the initialization phase, the analytemonitoring system is configured to calculate but not display analytelevels.